Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin

Yu Hua Tseng, Atul J. Butte, Efi Kokkotou, Vijay K. Yechoor, Cullen M. Taniguchi, Kristina M. Kriauciunas, Aaron M. Cypess, Michio Niinobe, Kazuaki Yoshikawa, Mary Elizabeth Patti, C. Ronald Kahn

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156 Scopus citations

Abstract

The insulin/IGF-1 (insulin-like growth factor 1) signalling pathway promotes adipocyte differentiation via complex signalling networks. Here, using microarray analysis of brown preadipocytes that are derived from wild-type and insulin receptor substrate (Irs) knockout animals that exhibit progressively impaired differentiation, we define 374 genes/expressed-sequence tags whose expression in preadipocytes correlates with the ultimate ability of the cells to differentiate. Many of these genes, including preadipocyte factor-1 (Pref-1) and multiple members of the Wnt signalling pathway, are related to early adipogenic events. Necdin is also markedly increased in Irs knockout cells that cannot differentiate, and knockdown of necdin restores brown adipogenesis with downregulation of Pref-1 and Wnt10a expression. Insulin receptor substrate proteins regulate a necdin-E2F4 interaction that represses peroxisome-proliferator-activated receptor γ (PPAR-γ) transcription via a cyclic AMP response element binding protein (CREB)-dependent pathway. Together these define a key signalling network that is involved in brown preadipocyte determination.

Original languageEnglish (US)
Pages (from-to)601-611
Number of pages11
JournalNature cell biology
Volume7
Issue number6
DOIs
StatePublished - Jun 1 2005

ASJC Scopus subject areas

  • Cell Biology

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    Tseng, Y. H., Butte, A. J., Kokkotou, E., Yechoor, V. K., Taniguchi, C. M., Kriauciunas, K. M., Cypess, A. M., Niinobe, M., Yoshikawa, K., Patti, M. E., & Kahn, C. R. (2005). Prediction of preadipocyte differentiation by gene expression reveals role of insulin receptor substrates and necdin. Nature cell biology, 7(6), 601-611. https://doi.org/10.1038/ncb1259